kava and Liver-Failure

Topics: Beverages; Drug Labeling; Europe; Herb-Drug Interactions; Herbal Medicine; Humans; Kava; Liver Failure; Phytotherapy; Plant Extracts

The widely used over-the-counter analgesic acetaminophen (APAP) is the leading cause of acute liver failure in the United States and due to this high incidence, a recent FDA Advisory Board recommended lowering the maximum dose of APAP. Kava herbal dietary supplements have been implicated in several human liver failure cases leading to the ban of kava-containing products in several Western countries. In the US, the FDA has issued warnings about the potential adverse effects of kava, but kava dietary supplements are still available to consumers. In this study, we tested the potential of kava extract to potentiate APAP-induced hepatocyte cytotoxicity. In rat primary hepatocytes, co-treatment with kava and APAP caused 100% loss of cell viability, while the treatment of kava or APAP alone caused ∼50% and ∼30% loss of cell viability, respectively. APAP-induced glutathione (GSH) depletion was also potentiated by kava. Co-exposure to kava decreased cellular ATP concentrations, increased the formation of reactive oxygen species, and caused mitochondrial damage as indicated by a decrease in mitochondrial membrane potential. In addition, similar findings were obtained from a cultured rat liver cell line, clone-9. These observations indicate that kava potentiates APAP-induced cytotoxicity by increasing the magnitude of GSH depletion, resulting in oxidative stress and mitochondrial dysfunction, ultimately leading to cell death. These results highlight the potential for drug-dietary supplement interactions even with widely used over-the-counter drugs.

Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Anti-Anxiety Agents; Cell Survival; Cells, Cultured; Dietary Supplements; Drug Synergism; Glutathione; Hepatocytes; Humans; Kava; Liver Failure; Male; Membrane Potential, Mitochondrial; Mitochondria, Liver; Oxidative Stress; Plant Preparations; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; United States

Topics: Complementary Therapies; Female; Humans; Kava; Liver Failure; Passiflora; Phytotherapy; Plant Preparations

We describe a case of acute liver failure and death associated with the use of a preparation containing the "natural" anxiolytic kava (Piper methysticum) and passionflower (Passiflora incarnata). The patient died after a report by the Therapeutic Goods Administration (TGA) warning of the potential for hepatotoxicity associated with the use of kava-containing products. The general public and alternative medicine practitioners need to be aware of the potential for non-prescription drugs to cause serious hepatic reactions.

Topics: Complementary Therapies; Fatal Outcome; Female; Humans; Kava; Liver Failure; Middle Aged; Passiflora; Phytotherapy; Plant Preparations

Topics: Animals; Anti-Anxiety Agents; Chemical and Drug Induced Liver Injury; Glutathione; Humans; Kava; Liver Failure; Plant Extracts

Botanical drugs are widely used and often contain highly active compounds. Kava root (Piper methysticum rhizoma), used frequently in Europe as a remedy against anxiety, contains kavapyrones with sedative effects. Seven case reports suggested the development of hepatitis after the intake of Kava.. We analyzed 29 novel cases of hepatitis along with Kava ingestion which occurred between 1990 and 2002 in addition to the seven already published case reports using a clinical diagnostic scale established for adverse hepatic drug reactions.. Hepatic necrosis or cholestatic hepatitis were noticed with both alcoholic and acetonic Kava extracts. The majority of the 29 patients and the additional seven published reports were women (27 females, nine males). Both the cumulative dose and the latency to when the hepatotoxic reaction emerged were highly variable. Nine patients developed fulminant liver failure, of which eight patients underwent liver transplantation. Three patients died, two following unsuccessful liver transplantation and one without. In all other patients, a complete recovery was noticed after the withdrawal of Kava. Pathophysiologically, both immunoallergic and idiosyncratic factors may be responsible.. The present report emphasizes the potentially severe hepatotoxicity of Kava which has recently led to the retraction of Kava-containing drugs by the pharmacovigilance authorities in Germany.

Topics: Acute Disease; Adult; Aged; Anti-Anxiety Agents; Chemical and Drug Induced Liver Injury; Female; Germany; Humans; Kava; Liver; Liver Failure; Male; Middle Aged; Product Surveillance, Postmarketing

Topics: Chemical and Drug Induced Liver Injury; France; Humans; Kava; Liver Cirrhosis; Liver Failure; Product Surveillance, Postmarketing

The use of potentially hepatotoxic herbal and dietary supplements is highly prevalent in the fulminant hepatic failure (FHF) patient population at our institution, and this subgroup of patients has a worse prognosis.. Retrospective case series. Settings An adult tertiary care university hospital and a Veterans Affairs hospital in Oregon.. All patients referred to the liver transplantation service for FHF from January 2001 through October 2002 (N = 20). We defined FHF as onset of encephalopathy within 8 weeks of onset of jaundice in the absence of preexisting liver disease. All patients underwent investigation for potential causes of liver injury. Potentially hepatotoxic supplements were defined as those with previously published reports of hepatic injury related to their use.. Ten patients (50%) were recent or active users of potentially hepatotoxic supplements or herbs; 10 had no history of supplement use. In the supplement group, 7 patients (35%) had no other identified cause for hepatic failure. Six patients in the supplement group and 2 patients in the nonsupplement group underwent orthotopic liver transplantation. Five patients in each group died. There were no significant differences in transplantation rate (P =.07) or survival (P>.99) between groups. Supplement use alone accounted for the most cases of FHF during this period, exceeding acetaminophen toxicity and viral hepatitis.. Herbal and dietary supplements were potential hepatotoxins in a high proportion of patients with FHF at our institution. Enhanced public awareness of the potential hepatotoxicity of these commonly used agents and increased regulatory oversight of their use is strongly urged.

Topics: Adult; Benzofurans; Benzopyrans; Caffeine; Chemical and Drug Induced Liver Injury; Dietary Supplements; Diiodothyronines; Drug Combinations; Ephedra sinica; Female; Humans; Kava; Larrea; Liver Failure; Liver Transplantation; Male; Middle Aged; Phenylpropanolamine; Plant Preparations; Prevalence; Retrospective Studies; Yohimbine

Topics: Adverse Drug Reaction Reporting Systems; Complementary Therapies; Drug Information Services; Herbal Medicine; Humans; Kava; Liver Failure; Medicine, African Traditional; Registries; South Africa

Topics: Humans; Kava; Liver Failure

Topics: Adolescent; Chemical and Drug Induced Liver Injury; Female; Humans; Kava; Liver Failure

A 60 year-old woman was admitted to hospital because of jaundice, fatigue, weight loss over several months and icteric skin. Because of progressive liver failure, concomitant renal failure and progressive encephalopathy she was transferred to an intensive care unit.. Biochemical tests revealed acute liver failure with high levels of total and conjugated bilirubin (30 mg/dl) as well as aspartate aminotransferase (921 IU/l) and alanine aminotransferase (1350 IU/l) concentrations. Prothrombin time was less than 10 %. Serological tests could rule out viral hepatitis, metabolic or autoimmune causes of liver failure. On abdominal computed tomography and ultrasonography no pathological changes were detected. Above all portal vein thrombosis, ascites, focal lesions of the liver and extrahepatic cholestasis could be excluded. Liver histology showed extensive hepatocellular necrosis with intrahepatic cholestasis.. The patient's physical condition deteriorated. She had to be intubated because of respiratory insufficiency and encephalopathy stage IV. Because of progressive liver failure under conservative treatment the patient received an orthotopic liver transplant 11 days after admission.. The exclusion of other causes and the histological diagnosis made Kava-Kava as the cause of acute liver failure most likely. This is the 18th case of Kava-Kava induced liver failure reported to the European regulatory authorities.

Topics: Alanine Transaminase; Antidepressive Agents; Aspartate Aminotransferases; Bilirubin; Female; Humans; Kava; Liver; Liver Failure; Liver Transplantation; Middle Aged; Phytotherapy; Plants, Medicinal; Portal Vein; Venous Thrombosis